Regulation of microglial cell function by ATP

: Accumulated evidence suggests that extracellular ATP functions occur in neurons and glial cells in the nervous systems. Besides well-documented roles as a neurotransmitter or neuromodulator, ATP has also been demonstrated to have effects on glial cells. Reports have shown that ATP stimulates microglia to release various biologically active substances, such as interleukin-1 beta, tumor necrosis factor-alpha, and plasminogen. Microglial cell death was also demonstrated after stimulation with high-dose ATP. Although these responses were known to occur, via P2X7, we have recently found that ATP and ADP induced the formation of membrane ruffles and chemotaxis through Gi/o-coupled P2Y receptors. Taken together, it is suggested that two distinct P2X and P2Y receptor subtypes are involved in the diverse function of microglia in both physiological and pathological states.